Tobacco use is associated with approximately 30 percent of all cancer deaths, and cigarette smoking remains the single most preventable cause of cancer and premature death in our society. Recent epidemiological studies have demonstrated a strong genetic component to smoking. Unfortunately, there has been a relative dearth of studies that have attempted to measure the physiological, hormonal, behavioral, or subjective responses that may objectively define the phenotype for smoking. Since these types of responses may figure importantly as mechanisms that mediate the genetic susceptibility for smoking, there is a pressing need for studies that examine differences among those at varying degrees of risk for smoking. The proposed research seeks to examine biobehavioral mechanisms that may underlie an increased genetic risk for smoking within a laboratory-based experimental paradigm. To accomplish this goal, we will examine men and women smokers' and never-smokers' psychophysiological, hormonal, self-report, and information processing responses to standard IV nicotine doses and how these responses relate to family smoking history. The focus will be on affective and attentional responses within these paradigms, since these are empirically and theoretically related to smoking behavior. We will also examine subjects' affective responses to standardized pictures after nicotine dosing. It is hypothesized that affective and attentional responses obtained after nicotine administration, including responses to affective and smoking- related cues, will be predictive of family smoking history. Research examining biobehavioral response to nicotine within a genetics framework has yet to be conducted and may lead to a better understanding of the mechanisms that mediate susceptibility for smoking. This increased understanding could lead to more effective prevention and treatment efforts for cigarette smoking, and consequently decrease the prevalence of cancer in our society.